PROJECT SUMMARY/ABSTRACT Stroke rehabilitation technologies and treatments must progress through multiple phases of research and development before they reach clinical acceptance and are translated to clinical practice. Progressing from single-site to multi-site clinical trials is a critical step in the process. Multi-site studies prove whether a technology and/or treatment can be successfully administered by sites other than the originating site and with similar positive outcomes. The study proposed here is the first multi-site clinical trial of a new intervention called contralaterally controlled functional electrical stimulation (CCFES). CCFES is an innovative technology and rehabilitation therapy for improving the recovery of hand function in patients with upper extremity hemiparesis. CCFES applies electrical stimulation to the paretic finger and thumb extensor muscles through surface electrodes, causing the weak hand to open, a function that is often lost in stroke survivors. The patient controls the intensity of stimulation to their paretic hand by wearing a glove with sensors on their unaffected contralateral hand. When the patient opens their unaffected hand, a proportional intensity of stimulation opens their paretic hand. CCFES puts the patient back in control of their paretic hand, and this may drive neuroplastic changes that lead to better recovery of hand function. CCFES therapy includes using the device to assist hand opening during functional task practice sessions with a therapist in the lab plus self-administering a CCFES- mediated repetitive hand opening exercise at home. Our previous single-site study showed that CCFES improves dexterity more than conventional cyclic NMES (cNMES) in chronic (> 6 months) stroke patients, and identified most likely responders to be stroke survivors who are less than 2 years post-stroke. The main purpose of this study is to confirm and demonstrate the generalizability of these preliminary results in a larger group of most likely responders across multiple sites. The study will enroll 171 stroke survivors who are 6 to 24 months post-stroke. They will be randomized to 12 weeks of CCFES, cNMES (which applies electrical stimulation to the hand extensors, but with pre-set timing and intensity), or task-oriented training without electrical stimulation. The study will be conducted by research teams at three sites, who will administer the treatments and blinded outcome assessments. This study will determine whether CCFES therapy produces greater improvements in upper extremity function than cNMES or task-oriented training, and explore the effects of CCFES therapy on the central nervous system. Retention of improvements will be evaluated through a 6- month post-treatment follow-up period. This Phase II multi-site study is a critical step in advancing a novel method of rehabilitation toward clinical translation and widespread dissemination.